Hand eczema is a prevalent skin disorder, encompassing a variety of diseases such as contact dermatitis and dyshidrosis (pompholyx) (Tamiya, Y. Nippon Ika Daigaku Zasshi 1994 61(4):286-94). Dyshidrosis is characterized by initial symptoms of blistering and dry cracked skin on the hands or feet, affecting the tips and sides of fingers, toes, soles and palms. The disease develops progressively into continual scaling, peeling, cracked skin, bleeding, deep fissures and open wounds that in many cases do not heal. Dyshidrosis exists as either a chronic or recurring condition and intermittent flare-ups tend to occur after extended periods of stress or emotional conflict. Although it is not known what causes the disease, dyshidrosis and other forms of hand dermatitis are thought to be related to stress, anxiety or contact with some form of irritant or allergen (Lehucher-Michel, M. P., Koeppel, M. C., Lanteaume, A., Sayag, J. Contact Dermatitis 2000 43 (4):200-5).
While topical steroidal or non-steroidal immuno-suppressive agents remain the primary treatment for dyshidrosis, atopic dermatitis and psoriasis, they don't address the etiology of the disease, leaving some individuals non-responsive to available prescriptive medicines. Moreover, local and systemic side effects are risks with extended use with prescriptive treatment. If the condition is non-responsive to medicine, lifestyle alterations for those suffering with pompholyx often include being confined to use of cotton lined gloves and avoiding direct contact with ubiquitous substances such as soap, water, detergents, paints, polish and chemicals. Moreover, there could be a potential loss of functional utility of the hands and/or feet. Open wounds require constant care to maintain asceptic conditions and careful applying of bandages. And, since soap and water worsen the condition of this disease, it becomes quite difficult to maintain a sterile environment proximal to the site of injury.
Options available to those diagnosed with pompholyx or related skin diseases, who do not respond to steroidal anti-inflammatory agents are quite limited. The use of standard ultraviolet (UV) therapy (WO 02/055149, Oct. 22, 2001, Irwin and Altman) and subsequent modifications have been patented to treat dyshidrosis (US-2002183811, Dec. 5, 2002, Irwin). UV therapy has been moderately successful and in patients with non-responsive forms of dyshidrotic eczema, approximately 31% establish complete remission, 33% exhibit partial remission and 36% exhibit no change (Douwes, K. E., Karrer, S., Abels, C., Landthaler, M., Szeimies, R. M. Photodermatol Photoimmunol Photomed 2000 16:25-9). For this reason, there is a need to investigate alternative natural topical agents to treat this and similar diseases of the skin, to which there are no effective treatments.
The embodied invention describes a useful formulation and method thereof, that has shown to effectively establish remission of dyshidrosis, non-responsive to prescriptive topical medicine. These are preliminary findings, and warrant further research and investigation. To date, there are no integrated topical herbal formulas described to treat dyshidrosis or similar conditions such as exfoliative keratolysis and palmoplantar pustulosis. There are, however, patented therapeutic approaches described to treat dyshidrosis with vitamin E analogues (WO-97/45098, Jun. 2, 1997, Panin), sulfhydryl acyl derivatives (U.S. Pat. No. 4,721,705, Jan. 26, 1988, Schreuder), oral administration of salts and esters of cis retinoic acid (U.S. Pat. No. 6,589,989, Jul. 8, 2003, Bollag, et al.) and topical steroids (U.S. Pat. No. 4,891,386, Oct. 15, 2002, Dykstra). Alternatives to treat pompholyx, have also included using an isolated extract derived from the bark of a southestern Asian plant called the citrus decumana tree (JP-6340541, Dec. 13, 1994, Tashiro Eiichi) and fresh pine needle (CN-1113795, Dec. 27, 1995, Chunyang et al.).
The embodied invention discloses a topical formulation and method of use, found effective in establishing complete remission in a pilot trial of severe dyshidrosis, non-responsive to current prescription medicines and over the counter ointments. Moreover, the method was found to be effective in rapidly suppressing and reversing initial symptoms of outbreak. Results indicate that therapy can be discontinued after remission is established. The principles governing development of the embodied formulation were based on observations regarding pathological symptoms of the disease: A) this skin disease stops at the perimeters of the hands and feet, indicating reduced circulation or blood flow may play a role B) this condition appears to involve an unknown factor, with an intermittent nature, that thrives on both moisture and flesh, possibly a virus C) this condition escapes capability of our immune system to destroy it and D) there is extensive skin loss, somewhat similar to a second degree burn. For these reasons, the method of use includes a topical ointment formulated to (1) contain anti-microbial: anti-parasitic, anti-bacterial, anti-protozoal, anti-fungal and anti-viral properties to destroy or inhibit the growth of invading pathogenic organisms or potential unknown retroviruses (2) contain dermal anti-inflammatory agents: effective cyclooxygenase inhibitors/lipoxygenase inhibitors, and compounds that attenuate local dermal eicosanoids and prostaglandins to reduce the swelling, redness and pain (3) contain cutaneous vasodilators that inhibit thromboxanes, and increase local endothelial nitric oxide to increase blood flow to the area of injury (4) contain aloe vera gel as a base in order to promote rapid healing of damaged or lost skin tissue and (5) contain compounds that destroy or remove dead skin, which appear to correlate with rapid healing. Application of oral intake of niacin can effectively increase blood flow to the area of injury to act synergistically with the topical formuation.
The embodied invention is unique and its formulation was based on pharmacological scientific principles rather than literature describing common herbs that are good for the skin. While there are a number of herbal creams on the worldwide market available for the treatment of skin disorders, few contain the active ingredients as described in this invention. Moreover, it has been reported that many marketed herbal topical skin products, either don't work or they are misleading, claiming to be natural, but adulterated with potent steroids. Interestingly, according to an article on Tuesday, 9 Dec. 2003 BBC News Entitled “Steroids in herbal eczema creams”, in a small scale study, 20 out of 24 herbal creams sold for treatment of eczema, contained potent steroid drugs, some labeled under the ingredient “Wau Wa”, components that were really pharmaceutical grade steroids in a paraffin base. The reporter indicated that he would be surprised if any “herbal cream could rapidly eradicate eczema”. There are also other reports that indicate a similar pattern where herbal creams sold over the counter, have been adulterated with agents such as topical zinc pyrithione or clobetasol propionate, which in some places are banned or illegal.
A review of the literature regarding skin creams that are sold and marketed, indicate that many herbal creams have analogous constituents, that are commonly known as skin remedies. Common ingredients in herbal skin creams include burdock, dandelion, lavender, marigold, marshmallow, nettle, violet, rosemary leaf, lemongrass, rosewood, sandlewood, yarrow, tea tree, geranium, chickweed, myrrh, yellow dock, golden seal, birch, calendula, echinacea, goldenseal, red clover, comfrey, and witch hazel or colloidal silver. Common herbal ointments include variations and combinations of these ingredients, such as, ZenMED natural eczema treatment system (zenmed-natural-herbal-eczema-treatment-cure.com), which contains the active ingredients borage oil, calendula, chamomile, viola, dog rose, echinacea, tea tree oil, vitamin A, C, E, bioflavonoids, kukui oil, lavender, geranium and tangerine. Another breakthrough herbal cream for eczema (Attogram Corp.), contains oils of cedarwood, chamomile, eucalyptus, lavender, palmarosa, rose, tea tree, castor, olive, colloidal silver, citric acid and lanolin. And, many variations have been described in herbal skin ointments such as combinations using comfrey, tea tree, witch hazel, dandelion, goldenseal, lavender, yellowdock (community-2.webtv.net), dandelion, goldenseal, red clover; yellow dock (sunthymeherbfarm.com), yellow dock, red clover or cleavers (viable-herbal.com), brewers yeast, nightshade and red clover (target.com), hawthorn, licorice, burdock, chamomile, ginkgo, gotu kola, echinacea, comfrey, dandelion, marshmallow, red clover etc. (herbs.org), goldenseal, kelp, myrrh, red clover, Pau d'arco, dandelion and yellow dock root (drcureme.com). The topical cream Florasone (herbalremedies.com) claims to be the first natural alternative to cortisone creams introduced in the United States and contains the active ingredient comprised of extract of Cardiospermum. And, other skin tonics such as those that treat herpes simplex, scabies, dermatitis, eczema and fungal infections are comprised of unique herbs such as cortex phellodendri, radix sophorae flavescentis, Rhuctus chidii and rhizoma atractylodis (herbalhealer.com).
According to a review of prior art, the embodied method is in terms of its unique combination of powerful ingredients, and specific utility to ameliorate dyshidrosis and similar skin disorders such as palmoplantar pustulosis and exfoliative keratolysis. The primary ingredients within the topical formula include a combination of dry, aqueous, acid or alcohol extracts of black walnut hull (Juglans nigra), wormwood (Artemisia absinthium), tumeric rhizome (Curcuma longa), garlic (Allium sativum), chamomile (Matricaria Chamomile), licorice root (Glycyrrhiza glabra), St Johns wort (Hypericum perforatum), aloe vera, one or more herbal antibacterial agents and niacin or its derivatives, where niacin can also be delivered orally. The combination of topical ingredients as a composite, was found to be lethal to bacteria, fungus, mold and yeast, indicating its use may include an expansive range of skin disorders associated with invasive pathogens. The formula is comprised of cooking spices and components that are often taken orally by humans, therefore the ingredients should be relatively safe, with exception of potential allergic sensitivity reactions that may occur such as that with use of topical garlic.
The following enclosed is an introduction of circumscribing prior art for each ingredient in the formula as it applies to topical applications of the skin, or mechanism of action involved with the dermal inflammatory response. First, extracts of wormwood or artemesia are often incorporated into complex formulas that comprise agents directly applied to the skin, such as aftershave lotion (RU-2109506, Apr. 27, 1998 Dolotovskij et al.), facial cleanser (RU-2124350, Jan. 10, 1999, Detsina et al.; CN-1236610, Dec. 1, 1999, Liu), wrinkle reduction cream (CN-1110132, Oct. 18, 1995, Zhongxin), muscle pain ointment (U.S. Pat. No. 6,579,543, Jun. 17, 2003, McClung), treatment for warts (U.S. Pat. No. 5,576,005, Nov. 19, 1996, Wise, et al.) and anti-aging formulas that promote synthesis of collagen (JP-206835, Jul. 31, 2001, Sasaki et al.).
Wormwood is known for its anti-parasitic effects, and if taken internally can promote bowel movement, improve digestion and enhance blood circulation. Previous research on therapeutic use for wormwood and artemisinin, primarily focus on its efficacy as an anti-malarial compound. There is little to no technical research, documenting the efficacy of wormwood, relevant to skin diseases. There are, however, topical agents patented for treatment of dry skin that have included wormwood as a minor component in a list of ingredients. Of these include: wormwood 1) listed with 12 other herbal constituents that comprise a secondary tincture to be combined with a primary herbal extract base consisting of rowan melanocarpous, bird cherry and rose fruit, and a pretreatment of Siberian fir coniferous needles and sea-buckthorn juice for treatment of dermatitis (RU-2124363, Jan. 10, 1999, Tereshchenko et al., 2) in combination with pine needle, dark plum, peppermint, acetic acid, borneol and bezoar, for treatment of dermatitis (CN-1360899, Jul. 31, 2002, Lan) 3) artemisia capillaris incorporated in to a base formula of ω3 and ω6 fatty acids as one of approximately 30 optional herbal extracts to treat dry skin, inflammation, rash and itching (JP-063942, Mar. 5, 2003, Shizuka et al., and 4) at very low concentration, (approx 0.1-0.5% wormwood) in combination with glycerine, propolis extract, oil of common origanum, polyethyleneoxide gel, egg yolks, horsetail decoction, bergenia, plantain, citric, salicylic acids, henx salts, benzoate for treatment of fungal and microbial infections of the skin (RU-2118152, Aug. 27, 1998, Detsina et al.). It has been reported that the tricyclic sesquiterpene, artemisinin and its derivatives (chemicals found naturally in wormwood) may be effective in treating psoriasis, dermatitis, dyshidrosis and eczema (U.S. Pat. No. 5,057,501, Oct. 15, 1991, Thornfeldt). These findings indicate that beneficial effects observed in treatment of pompholyx, may be due to artemisinin and related chemicals within the extract of wormwood.
Black walnut (Juglans nigra). While the toxicity of black walnut in equine has been investigated, there is little to no research documenting the use of Juglans nigra to treat either infectious or non-infectious skin disorders. Further, there is meager patent literature describing the use of black walnut or Juglans nigra incorporated into topical creams or cosmetics, with exception of its use as a germicidal agent incorporated into chewing gum, deodorant gel and foot powder (U.S. Pat. No. 5,137,717, Aug. 11, 1992, Wixforth). Although there is little documentation in either research or patented literature, historical herbal literature indicates that black walnut is known to treat intestinal parasites, worms, warts, growths, eczema, psoriasis, lupus, herpes, and skin parasites. Interestingly, black walnut is not a common ingredient amongst herbal preparations marketed or sold for treatment of skin.
St. John's wort (Hypericum perforatum) is often incorporated into topical formulas that comprise a number of products including weight loss cream (U.S. Pat. No. 4,795,638, Jan. 3, 1989, Ayache et al.), anti-aging cosmetic (U.S. Pat. No. 4,911,925, Mar. 27, 1990, Shatkina et al.), lotion (EP-1291011, Mar. 12, 2003, Leonidov et al; RO-116865, Jul. 30, 2001, Ionita-Manzuta et al.), facial cleanser (U.S. Pat. No. 6,342,208, Jan. 29, 2002, Hyldgaard et al.), topical treatment for acne and chapped skin (JP-04-124138, Apr. 24, 1992, Yan et al.), burn ointment (CN-1179950, Apr. 4, 1998, Mo Xiaochun), treatment for fungal infections of the nail (GB-2311009, Sep. 17, 1997, Khan Mohd Taufiq) muscular pain relief lotion (U.S. Pat. No. 6,579,543, Jun. 17, 2003, McClung), arthritis pain reliever (U.S. Pat. No. 6,573,302, Jun. 3, 2003, Holt et al.), moisturizer (JP-60-258104, Dec. 20, 1985, Yuchi et al., and lotions with smoothing, firming and UV protection properties (U.S. Pat. No. 5,560,917, Oct. 1, 1996, Cohen et al.).
St. John's wort has also been used in the past, as a remedy to treat wounds and burns (Schempp C M, Muller K A, Winghofer B, Schopf E, Simon J C. Hautarzt. 2002 May; 53(5):316-21). Hyperforin, a primary constituent of St. John's wort is effective in treating atopic dermatitis (Schempp C M, Windeck T, Hezel S, Simon J C., Phytomedicine. 2003; 10 Suppl 4:31-7.), possibly through anti-inflammatory properties (Schempp C M, Winghofer B, Ludtke R, Simon-Haarhaus B, Schopf E, Simon J C., Br J Dermiatol. 2000 May; 142(5):979-84). St. John's wort has also been used as a constituent in topical agents for treatment of dry skin as it relates to photo damage effects of the sun. Of these, include its use in combination with branches and leaves of olive, glycyrrhetinic acid and allantoin (JP-183146, Jul. 3, 2003, Hikima et al.) and in combination with asparagus extract, chamomile, Lithospermum erythrorhizon, Lonicera japonica, sage, birch, Calendula officinalis, elder tree, flag, glycyrrhizic acid, guaiazulene, aminocaproic acid and their derivatives (JP-06-128145, May 10, 1994, Hayashi et al.).
Relevant prior art pertaining to the use of St. John's wort include 1) the use of extracts of St John's wort depleted of chlorophyll for treatment of acne, viral infections and psoriasis (DE-10131641, Jun. 27, 2002, Koch et al.,) 2) its use with or without Tilia miqueliana extract to treat contact dermatitis, allergic skin reactions and rough skin (JP-09-157176, Jun. 17, 1997, Nishibe) and 3) St. John's wort added to a base formula of (ω3 and (ω6 fatty acids, as one of 30 optional herbal extracts to treat dry skin, inflammation, rash and itching (JP-063942, Mar. 5, 2003, Uehara Shizuka et al.).
Tumeric (Curcuma longa) has been incorporated into topical skin lightening and UV protective lotion (WO 03/030814, Apr. 17, 2003, Muhammed et al.), treatment for acne (CA-2353057, Jan. 13, 2002, Khaiat; U.S. Pat. No. 6,277,881, Aug. 21, 2001, Santhanam et al.), treatment for skin discoloration and hemorrhoids (U.S. Pat. No. 6,048,533, Apr. 4, 2000, Nguyen Van Bich), ointment that relieves soreness and muscle discomfort (U.S. Pat. No. 6,579,543, Jun. 17, 2003, McClung), lotion that protects against environmental toxins (U.S. Pat. No. 6,521,668, Feb. 18, 2003, Anderson et al.) and treatment for wounds and ulcers (U.S. Pat. No. 5,401,504, Mar. 28, 1995, Das et al.).
Turmeric is an anti-inflammatory agent and when applied to the skin, has shown to reduce dermal inflammatory promoters such as arachidonic acid, cyclooxygenase, lipoxygenase 5-hydroxyeicosatetraenoic acid and pro-inflammatory prostaglandins (Huang, M. T., Lysz, T., Ferraro, T., Abidi, T. F., Laskin, J. D., Conney, A. H. Cancer Res 1991 51:813-9.; Huang, M. T., Newmark, H. L., Frenkel, K. J Cell Biochem Suppl 1997 27:26-34). Curcumin also contains inherent antiviral properties (Barthelemy, S., Vergnes, L., Moynier, M., Guyot, D., Labidalle, S., Bahraoui, E. Res Virol 1998 January-February; 149(1):43-52; De Clercq, E. Med Res Rev 2000 20:323-49) and is effective against tumor promoting viral agents, such as Epstein-Barr virus and herpes simplex virus type 2 (Kapadia, G. J., Azuine, M. A., Tokuda, H., Hang, E., Mukainaka, T., Nishino, H., Sridhar, R. Pharmacol Res 2002 45:213-220.; Boume, K. Z., Boume, N., Reising, S. F., Stanberry, L. R. Antiviral Res 1999 42:219-26). Moreover, turmeric has a number of other pharmacological properties such as anti-bacterial, anti-parasitic and antispasmodic (Araujo, C. C., Leon, L. L. Mem Inst Oswaldo Cruz 2001 96:723-8).
Prior art describing the use of turmeric as a constituent in topical agents for treatment of dry skin include: its use as a minor ingredient 1) in combination with hydroxy acids, vitamin E, vitamin B, glycolic acid, antioxidants, hormones, and oils to treat psoriasis, dryness, itching, stretch marks, and microbial infections (US-App # 2003113388, Jun. 19, 2003, Phan) 2) in combination with triclosan, phenoxy ethanol, benzalkonium chloride, benzethonium chloride, cocophosphatidyl-dimonium chloride for the treatment of skin inflammations, redness, pain, exudate, and bacterial infections (U.S. Pat. No. 6,248,343, Jun. 19, 2001, Jampani et al.), 3) at a low concentration (0.1-1%), as an optional anti-inflammatory compound incorporated into a base of carbopol, emulsifiers, preservatives, and humectants containing Tridax procumbens extract and gum olibanum powder the treatment of cracked heels, dry skin disorder, skin allergies, depigmentation, burns, wounds and fungus (U.S. Pat. No. 6,379,673, Apr. 30, 2002, Diwan et al.) 4) in combination with ω3 and ω6 fatty acids for treating dry skin, inflammation, rash and itching (JP-063942, Mar. 5, 2003, Uehara Shizuka et al.,) 5) incorporated as an optional ingredient selected from a list of herbs into a base of dihydric alcohol solution, as an antibacterial skin preparation (JP-145793, Mar. 22, 2002, Kobayashi Kayoko et al.,) and 6) in combination with a base comprising hydroxy acid and retinol deriviatives, for treating skin inflammation and irritation (JP-002559, Jan. 9, 2001, Santanamu et al.,). In documents where turmeric comprises a primary component, (JP-09-143086, Jun. 3, 1997, Masayoshi), a fat-soluble extraction procedure for turmeric has been described, introducing a carrier system of vegetable oil for treatment of skin diseases such as eczema, acne, atopic dermatitis, chapped skin or general.
Propolis is an optional ingredient in this formula. It was not incorporated into the base formula as tested, however, it may be used as a substitute to replace ingredients that may otherwise cause allergic skin reactions such as garlic, or to enhance efficacy or aesthetic properties. Propolis has been used in formulations that comprise beauty lotion, or regenerative skin cosmetic (RU-2166313, May, 10, 2001, Dolotovskij et al.), deodorizer (RU-2185808, Jul. 27, 2002, Khismatullin), moisturizing cream (RU-2161029, Dec. 27, 2000, Kravchenko; JP-10-194948, Jul. 28, 1998, Yamamoto), wrinkle removing cream (RU-2161029, Dec. 27, 2000, Zhang; CN-1268348, Oct. 4, 2000, Tong), bug repellent, skin cleanser, germicide (CN-1263146, Aug. 16, 2000, Liu Fuhai Xu et al.) exfoliation cream (U.S. Pat. No. 6,416,769, Jul. 9, 2002, Vromen), skin whitener (U.S. Pat. No. 6,269,817, Aug. 7, 2001, Nagashima et al.) tanning solution (U.S. Pat. No. 6,171,605, Jan. 9, 2001, Bevacqua et al.) burn ointment (JP-07-304684, Nov. 21, 1995, Longchamp), treatments for acne and dandruff (JP-59-118702, Jul. 9, 1984, Takashi et al.) and treatment for skin fungal infections, such as candidiasis (RU-2118152, Aug. 27, 1998, Detsina).
There is documented evidence that topical application of propolis can aid in the healing of burn wounds (Gregory, S. R., Piccolo, N., Piccolo, M. T., Piccolo, M. S., Heggers, J. P. J Altern Complement Med 2002 8:77-83). Moreover, propolis has several medicinal properties, including it ability to serve as an analgesic, anti-flammatory agent, and ameliorate symptoms of psoriasis (Ledon, N., Casaco, A., Gonzalez, R., Merino, N., Gonzalez, A., Tolon, Z. Zhongguo Yao Li Xue Bao 1997 18:274-6; Park, E. H., Kahng, J. H. Arch Pharm Res 1999 22:554-8). Propolis is also a powerful antibacterial and antifungal agent, with efficacy demonstrated against a large variety of pathogens (Ota, C., Unterkircher, C., Fantinato, V., Shimizu, M. T. 2001 44:375-8; Drago, L., Mombelli, B., De Vecchi, E., Fassina, M. C., Tocalli, L., Gismondo, M. R. J Chemother 2000 12:390-5; Koo, H., Gomes, B. P., Rosalen, P. L., Ambrosano, G. M., Park, Y. K., Cury, J. A. Arch Oral Biol 2000 45:141-8).
Propolis as a constituent has been used in topical agents for treatment of dry skin and/or bacterial infections, some of which include its use 1) in combination with an inert base, amica montana, woody aloe, marigold and at least one antibiotic selected from detromycin, bacitracin, neomycin, polymyxin etc. for ameliorating burns (WO 02/076411, Oct. 3, 2002, Dorian) 2) in combination with olive oil, sea buckthorn-seed oil, beeswax, dog rose oil, St. Johns wort oil extract, peony root oil extract, bergenia oil extract to treat wounds (RU-2195258, Dec. 27, 2002, Repjakh) 3) in combination with honey, apricot seed extract and royal jelly to treat discoloration, wounds, burns, miliaria and eczema (KR-20010008260 A, May 2, 2001, Kim), 4) in combination with Balsaminaceae to treat skin allergies and atopic dermatitis (JP-11-322620, Nov. 24, 1999, Sakamoto et al.) 5) in combination with pyrolignous acid, chitin chitosan and garlic for treatment of parasitic atopic dermatitis, athlete's foot, scabies, dermatophytosis, candidiases, scabies, tinea cruris or serpigo (JP-10-175878, Jun. 30, 1998, Otsuka et al.) and 6) in combination with alcoholic-glyceric nettle, chelidonia, oak bark, willow bark, calendula, dandelion roof, camomile, achillea, dill, parsley, thyme oil, lemon oil etc, for treatment of psoriasis (WO 01/66079, Feb. 28, 2001, Bodnar et al.).
Chamomile (Matricaria Chamomile) has been incorporated into topical anti-pollution cream (U.S. Pat. No. 5,571,503, Nov. 5, 1996, Mausner), a cosmetic (U.S. Pat. No. 6,299,890, Oct. 9, 2001, Russ et al.), lotion (U.S. Pat. No. 6,589,514, Jul. 8, 2003 Jensen et al.), moisturizer (U.S. Pat. No. 6,579,516, Jun. 17, 2003, Mansouri), tanning solution (U.S. Pat. No. 6,482,397, Nov. 19, 2002, Scott et al.), exfoliation cream (U.S. Pat. No. 6,416,769, Jul. 9, 2002, Vromen), anti-aging and whitening cream (U.S. Pat. No. 5,393,526, Feb. 28, 1995, Castro), skin cleanser (U.S. Pat. No. 6,221,372, Apr. 24, 2001, Golz-Bemer et al.) acne treatment (CA-2353057, Jan. 13, 2002, Khaiat), revitalizing, smoothing, moisturizing cream (U.S. Pat. No. 5,876,736, Mar. 2, 1999, Cohen et al.), arthritic pain reliever (U.S. Pat. No. 5,869,533, Feb. 9, 1999, Holt), cuticle and nail ointment (WO 03/047537, Jun. 12, 2003, Beaurline) and aftershave lotion (U.S. Pat. No. 4,758,599, Jul. 19, 1988, Minetti).
Chamomile has been incorporated into topical agents with dozens of other ingredients, for treatment of dry skin disorders. These include its use 1) in combination with Althaea officinalis L., Malva flowers, Tillia platyphyllos and Achillea millefolium L. for treatment of skin inflammation, excoriations, ulcers (WO 03/033007, Apr. 24, 2003, Baraldi) 2) in combination with Chelidonium majus L, Plantago major L, Plantago media L, Convallaria majalis L, may flower honey, raw egg, gum-tree oil, lanolin for treatment of atopic dermatitis, urticaria and eczema (RU-2107510, Mar. 27, 1998, Labutin et al) 3) in combination with propylene glycol, acids, alcohols, carbomer, tea tree, amino acids, etc., for treating psoriasis (U.S. Pat. No. 6,403,654, Jun. 11, 2002, De Oliveira) 4) in combination with plantago major, yarrow, olive oil, eucalyptus, calendula for treatment of burns and wounds (U.S. Pat. No. 5,997,876, Dec. 7, 1999, Shikhashvili et al.) and 5) in combination hamamelis, almond oil, olive oil, and myrrh with for treatment of abrasions broken skin, cuts, cold sores, bed sores and piles (U.S. Pat. No. 5,350,774, Sep. 27, 1994, Palou).
Garlic (Allium sativum) or deodorized garlic has been incorporated into weight loss cream (US-2002146474, Oct. 10, 2002, Tomatis), anti-aging cream (KR-2002019716, Mar. 13, 2002, Choi et al.), depilatory cream (CN-1398578, Feb. 26, 2003, Wu), general skin protective lotion (CN-1378835, Nov. 13, 2002, Gu et al.), an analgesic (U.S. Pat. No. 6,579,543, Jun. 17, 2003, McClung) rejuvenation cream (JP-09-328417, Dec. 22, 1997, Morinaga), body rinse (JP-08-165233, Jun. 25, 1996, Kuroiwa et al.), moisturizer (JP-07-133208, May, 23, 1995, Okada) skin peel (JP-54044082, Apr. 7, 1979, Tsukada et al.) and treatment for head lice (U.S. Pat. No. 6,103,248, Aug. 15, 2000, Burkhart et al.) and hairloss (U.S. Pat. No. 4,855,131, Aug. 8, 1989, Iris).
The effects of garlic on the skin have been reported specific to psoriasis. For example, (U.S. Pat. No. 6,153,197, Nov. 28, 2000, Albazi et al.) discloses a mixture of garlic and radish plant in dilute acetic acid to treat psoriasis. Garlic in combination with plumbago europaea (DE-10126023, Dec. 12, 2002, Karassalidou-Mueller) and urtica dioica, common nettle/, chelidonium majus, milkweed, veronica officinalis, veronica, calendula officinalis, calendula or marigold, achillea herba, millefolium, yarrow, fumaria officinalis are also effective against psoriasis (U.S. Pat. No. 5,165,932, Nov. 24, 1992, Horvath). And, mixtures of garlic with oil of celery seed, ceresin, Tween 80, castor oil and salicylic acid have been described for treatment of psoriasis (GB-842404, Jul. 27, 1960, Braun Ernest).
Garlic has been incorporated into topical agents with a list of other ingredients, for treatment of dry skin disorders. These include its use 1) as an optional ingredient amongst others in a base mixture with eperisone and tolperisone for the treatment of itching and dermatitis (JP-143513, May, 23, 2000, Manabe) 2) as an oil form (1-3% wt), incorporated into a base gel containing carbopol, emulsifiers, preservatives, humectants, anti-inflammatory compounds and optional ingredients such as Tridax procumbens extract and gum olibanum powder for treatment of cracked heels, dry skin disorders and skin allergies (U.S. Pat. No. 6,379,673, Apr. 30, 2002, Diwan et al.) 3) its use as a primary ingredient to treat infectious skin diseases (WO 02/089826, Nov. 14, 2002, Bhatham et al.,) and 4) in combination with propolis, pyroligneous acid and chitin to treat a large range of skin infections including, dermatophytosis, candidiases, scabies, tinea and others (JP-175878, Jun. 30, 1998, Otsuka Yuzaburo et al).
Licorice (Glycyrrhiza glabra) has been incorporated into topical agents have been described for treatment of acne (CN-1377686, Nov. 6, 2002, Zhang; JP-11-100324, Apr. 13, 1999, Sugimoto et al.), burn and sunburn ointment (CN-1348789, May, 15, 2002, Yang), protection against environmental aggressors (U.S. Pat. No. 6,649,178, Nov. 18, 2003, Mohammadi et al.), cleanser (JP-096492, Apr. 3, 2003, Suzuki), an anti-aging formula (JP-034631, July, Feb. 7, 2003, Honda; JP-370960, Dec. 24, 2002, Ueno et al.), a whitening agent (JP-284626, Oct. 3, 2002, Miki; JP-247442, Sep. 11, 2001, Maeda et al.), collagen synthesis promoter (JP-206835, Jul. 31, 2001, Sasaki et al.) and makeup (JP-09-052814, Feb. 25, 1997, Futaishi).
Licorice has steroidal like properties, and for that reason, should be incorporated into the formula with discretion. Licorice has been previously incorporated into topical agents with dozens of other ingredients, for treatment of dry skin disorders. These include its use 1) in combination with almond extract, sterol esters of a 10-26 C α-hydroxy fatty acid (JP-255780, Sep. 11, 2002, Yamashita) 2) with siberian fir coniferous needles, sea-buckthom juice, rowan melanocarpous, and many other herbal components (RU-2124363, Jan. 10, 1999, Tereshchenko et al.) 3) with tannic acid and carrageenan (U.S. Pat. No. 5,198,217, Mar. 30, 1993, Vedros) 4) with extracts of Marigold, Horse-chestnut, silver-weed, Walnut-tree leaves, Lavender and Roman chamomile oil (U.S. Pat. No. 5,080,901, Jan. 14, 1992, Ranky Nee Szita Katalin et al.) 5) with hydrocarbons, esters, triglycerides, fatty acids, surfactants, antiseptics, ultraviolet absorbers (JP-10-194949, Jul. 28, 1998, Sugiyama et al.) and 6) with extract of Sarcodon aspratus (Berk.) S. stearyl glycyrrhetate and dipotassium glycyrrhetate (JP-151689, Jun. 5, 2001, Kawamoto et al.).
Niacin, has been incorporated into cosmetics and other topical applications such as weight loss cream (WO 98/00101, Jun. 27, 1997, Pinotti et al.), arthritic pain relief ointment (US-2003125303, Jul. 3, 2003, Kucharchuk), skin lightening agent (U.S. Pat. No. 4,096,240, Jun. 20, 1978, Mathur; CA-2147262, May 11, 1994, Harding et al.) pigmentation formula (JP-, 10-059839, Mar. 3, 1998, Imahori), UV protectants (WO 02/03942, Jul. 6, 2001, Barclay), aftershave lotion (U.S. Pat. No. 4,758,599, Jul. 19, 1988, Minetti) and treatment for acne (GB-2210789, Jun. 21, 1989, Morrison), chapped skin, aging (JP-63-174911, Jul. 19, 1988, Sato; CA-2251790, Oct. 30, 1997, Oblong et al.) and dandruff (JP-63-060910, Mar. 17, 1988, Kawajiri et al.,).
Synthesized esterified nicotinamide derivates have been described for treatment of many diseases including cardiovascular, inflammatory, dermatological disorders, baldness, diabetes, cancer, and a method for the management of chemotherapy (NZ-306510, Jan. 18, 2000, Redden et al. and CA-2220091, Nov. 7, 1996, Manku et al.). Moreover, niacin has been used in conjunction with other constituents in topical agents to treat dry skin disorders. These include its use 1) in combination with nitrous oxide, essential fatty acids and Liquor Picis Carbonis [coal tar] to treat psoriasis, shingles, fever blisters, chicken pox, ache, chilblains, eczema, chloasmas, alopecia, dermatitis, ringworm and burn wounds (U.S. Pat. No. 5,633,284, May 27, 1997, Meyer) and 2) in combination with methylparaben, coconut oil, glycerine, polysorbate 60, vitamins etc, for treatment of psoriasis (CA-2027600, Apr. 16, 1992, Tosti).
Relevant art describing the use of niacin as the primary active constituent in topical formulations to treat skin disorders include its use as 1) esters of nicotinamide and nicotinic acid for treatment of acne, wrinkles, age spots, itching, pain, fungal infections, flaky dry skin, dandruff, seborrheic dermatitis, psoriasis and burns (U.S. Pat. No. 6,248,763, Jun. 19, 2001, Scivoletto) 2) as nicotinamide analogs to treat psoriasis, ichythyiosis, common warts, keratoacanthoma, seborrhoic keratosis and seborrhea (US-2003032617, Feb. 13, 2003, Bloch et al.) 3) niacin derivatives where delivery has been improved for penetration into the skin (U.S. Pat. No. 6,528,071, Mar. 4, 2003, Vatter et al.) and 4) incorporated into emulsions of microparticulates containing vitamin B3 for better delivery (U.S. Pat. No. 6,551,604, Apr. 22, 2003, Beck et al.). In this invention, we include oral intake of niacin due to its flushing vasodilatory effects, which should augment blood flow to the area of injury internally to provide greater therapeutic effect of the topical formulation.
Aloe has well known effects on the skin, including positive effects on cell regeneration and growth of epidermal tissue. (Choi, S. W., Son, B. W., Son, Y. S., Park, Y. I., Lee, S. K., Chung, M. H. Br J Dermatol 2001 45:535-45). Aloe can increase blood flow to the skin, and promote rapid healing of damaged skin tissue (Somboonwong, J., Thanamittramanee, S., Jariyapongskul, A., Patumraj, S. Med Assoc That 2000 83:417-25; Visuthikosol, V., Chowchuen, B., Sukwanarat, Y., Sriurairatana, S., Boonpucknavig, V. J Med Assoc That 1995 78:403-9). One of the major therapeutic properties of aloe, include its ability to increase collagen, dermatan sulphate and glycosaminoglycans (Chithra, P., Sajithlal, G. B., Chandrakasan, G. Mol Cell Biochem 1998 181:71-6; Chithra, P., Sajithlal, G. B., Chandrakasan, G. Indian J Exp Biol 1998 36:896-901; Chithra, P., Sajithlal, G. B., Chandrakasan, G. J Ethnopharmacol 1998 59:179-86).